The Barbara Ann Karmanos Cancer Institute

Targeting the MLN64/STARD3-cholesterol axis disrupts tight junction remodelling and attenuates gastric cancer aggressiveness

Introduction Gastric cancer remains a major cause of cancer-related mortality, largely due to invasion, metastasis, and therapeutic resistance. Dysregulated cholesterol metabolism is increasingly recognised as a driver of gastric cancer progression, but how intracellular choleste...

Obstetric and thrombotic outcomes among pregnant patients with myeloproliferative neoplasms: a propensity score matched real-world analysis

Pregnancies complicated by BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are associated with increased maternal and thrombotic risk; however, large real-world comparative data remain limited. We performed a multicenter retrospective propensity score-matched cohort study...

BUB1B Mitotic Kinase Dependency Reveals CENP-E Inhibition as a Tractable Approach for Castration and Enzalutamide Resistant Prostate Cancer

Abstract Castration-resistant prostate cancer (CRPC) progression despite treatment with potent androgen receptor (AR) antagonists such as enzalutamide is a major clinical challenge. The mitotic kinase BUB1B is a central member of an oncogenic seven-gene network that drives CRPC....

Interplay between fibroblast growth factor 9 (FGF9) and CD44 underlies 46,XY disorders of sex development in Kruppel‐like factor 1 (KLF‐1)‐E325K‐associated congenital dyserythropoietic anaemia (CDA‐IV)

Summary A heterozygous Kruppel‐like factor 1 (KLF1) E325K mutation causes a severe form of congenital dyserythropoietic anaemia (CDA), designated CDA‐IV (Online Mendelian Inheritence in Man, OMIM 613673), a rare disease with only 15 cases known. In addition to haemolytic anaemia,...

Breast cancer risk, epigenetic aging and DNA methylation clocks

Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death among women in the United States, and is globally a common and impactful cancer. Its distinct molecular subtypes, each defined by characteristic genomic and epigenomic profiles, var...

Proteogenomic profiling defines progression-associated biology in high-risk endometrial cancer

Patients with high-risk endometrial carcinoma (HR-EC) experience substantial mortality despite multimodality therapy, molecular classification and contemporary care. We determined whether proteomic tumor programs capture lethal risk beyond established clinical and genomic classif...

Genomic and Transcriptomic Landscapes of MEN1-Wild-Type Low-Grade Metastatic Pancreatic NETs Uncover Key Oncogenic Drivers and Targetable Pathways

Sporadic pancreatic neuroendocrine tumors (pNETs) with wild type MEN1 represent a major yet largely ignored subset whose biology and metastatic potential remain poorly understood. Because metastasis can occur despite low histologic grade and modest mutational burden, we hypothesi...

Single-nuclei RNA sequencing reveals obesity-associated rewiring of estrogen signaling in endometrioid adenocarcinoma

Endometrioid adenocarcinoma has one of the strongest body mass index associations of any solid tumor. This is widely attributed to amplification of estrogen-driven signaling via increased production of unopposed estrogen in peripheral adipose tissue. However, there is little evid...

A compendium of next-generation patient-derived models for diverse cancers

Abstract The development of new therapeutics and the validation of pathogenetic cancer mechanisms require representative laboratory models 1,2 . However, existing collections represent only a fraction of the diversity observed in human cancer 2–4 . Recent technologies have enable...